13948
J. Phys. Chem. 1995,99, 13948-13954
Hydroxylation by Electrochemically Generated O H Radicals. Mono- and Polyhydroxylation of Benzoic Acid: Products and Isomers' Distribution Mehmet A. Oturan* and Jean Pinson Laboratoire d'Electrochimie Moltculaire, UniversitC Denis Diderot-Paris 7, Unit6 Associte au CNRS no. 438, 2 Place Jussieu, 75251 Paris Cedex 05, France Received: March 21, 1995; In Final Form: July 17, 1995@
The electrochemical Fenton reqction (simultaneous reduction of dioxygen and ferric ions) permits a controlled production of OH' radicals. These are used for the stepwise hydroxylation of benzoic acid to mono- and polyhydroxylated products. The quantitative distribution of all the hydroxylated products is achieved by use of HF'LC. The overall reaction scheme is established and the rate constants of the individual steps are measured.
Introduction Oxygen radicals are very reactive species which are involved in a number of fields: chemistry (astrochemistry, environmental chemistry), biology, and medicine. I-' Among these radicals (02'-OH', , H O i , ROO', ...), the hydroxyl radical, OH', is certainly the most reactive. It is a very strong one-electron oxidizing agent: Eo(OH',H+M20)= 2.72 V/NHE* at pH = 0 and Eo(OH'/OH-) = 1.89 V/NHE,9-10which however seldom reacts as an electron transfer reagent. On the contrary, it is a very reactive reagent in hydrogen atom abstractions and in electrophilic additions.I I Some typical rate constants concerning these last reactions are shown in Table 1;12 they are close to the diffusion limit. If one considers the reactions of OH' with aromatic compounds, addition reactions are observed and not oxidations. Let us consider 1,2,4-trimethoxybenzene as an example. Its oxidation potential, E" = 1.13 VNHE, has been measuredI3 by pulse radiolysis in water. Compared with the redox potential given above for the OH'/OH- couple, one should expect a diffusion-controlled oxidation of the substrate; however, an addition of the hydroxyl radical is observedI4 with a rate constant k = 8.1 x lo9 M-' s-l. This must be related to the slowness of the electron transfer, which is not unlikely in view of the large solvent reorganization expected to follow this electron transfer. The very complex addition mechanism of OH' on aromatic derivatives has been investigated (benzene,15-20toluene,16-17.21-23 anisole,22fluorobenzene,22benzonitrile,22chl~robenzene,~~ nit r o b e n ~ e n e ,metho~ybenzenes,'~ ~~,~~ phenol,25benzoic acid and benzoate ion?7-31 salicylic acid,29,33.34 4-hydroxybenzoic acid,35 phenylacetic acid,I7 diphenylf~ran~~). The first step of this mechanism is a very fast nucleophilic additionI2 ( k = lo9 to 1Olo M-' s - I ) of the OH' radical on the aromatic ring, leading to the formation of an intermediate cyclohexadienyl radical (B), which has been detected under different conditions both by UV14,15,25.35 and ESR27,37spectroscopy. This radical undergoes different reactions depending on the medium in which it is formed. These reactions are summarized in Scheme 1. In the absence of an oxidizing reagent the main reactions are d i m e r i z a t i ~ n l ~ , 'and/or ~ * ' ~ . dismutation.16%22 ~~ In the presence of an oxidizing agent such as Fe3+ or Cu2+,the radical (B) is rapidly oxidized to the hydroxylated derivatives. 16-24-26-32-35 In an acidic medium, the hydroxycyclohexadienylradical (B) gives a radical cation (D) through an acid-catalyzed water elimination.'7.18.22.25.32 The radical cation can be reduced back to the @
Abstract published in Advance ACS Abstracts, September 1, 1995.
0022-365419512099-13948$09.00/0
TABLE 1: Rate Constants subsrate H'abstraction CzH50H CHzOHCHzOH
addition
benzoate ion benzoic acid p-aminobenzoate p-hydroxybenzoate phenol
k (M-] s-l) 1.9 x 1.8 x 5.9 x 4.3 x 1.1 x 8.9 x 1.4 x
lo9 lo9 109 109 1Olo
lo9 10"
conditions pH=6-7 pH=7 PH = 6-7 PH C. 3 pH = 7-9 pH = 7-9 pH = 7.4-7.7
SCHEME 1. Mechanism of the Addition Reaction of the OH. Radical on an Aromatic and Further Reactions of the Cyclohexadienyl Radical
R
hydroxylated dariuatives(0-,m-,p-)
tD
produds
starting material or undergo further reactions. In the presence of oxygen15~17.18,20,33.34,36,38 one observes the formation of the final hydroxylated aromatic either by formation of an intermediate peroxy radical (Dorfman mechanism) or through the formation of an intermediate dihydro diol in nonpolar solvents. The hydroxycyclohexadienyl peroxyl radicals obtained by addition of dioxygen on the cyclohexadienyl radical may again react with dioxygen to furnish endoperoxyl radicals which lead to ring-opened compounds.20 Therefore, the fate of the cyclohexadienyl radical depends to a large extent on the medium in which it is formed and therefore on the way hydroxyl radicals are generated. The production of hydroxyl radicals can also be achieved by the Haber-Weiss reaction: 1,39940
0 1995 American Chemical Society
J. Phys. Chem., Vol. 99, No. 38, 1995 13949
Mono- and Polyhydroxylation of Benzoic Acid
0;-
+ H,O,
-
HO'
+ OH- + 0,
(1)
(but its rate constant is too slow ( k = 0.13 L mol-' s-') to account for a significant production in biological sytstems), by radiolysis,' 5.20-29,35 by p h o t ~ l y s i s , ~ 'and - ~ *by~ ~the ~ ~Fenton ~~ reaction: which produces hydroxyl radicals'7-'9s33.34.36 through the reduction of hydrogen peroxide by Fez+: H,O,
+ Fez+ - HO' + OH- + Fe3+
80.- --20---
(2)
As indicated in Scheme 2, electrochemistry permits production of hydrogen peroxide directly in the solution by reduction of oxygen and at the same time to regeneration of Fez+, which can thus be used in a catalytic fashion.'9.33.43-50Setting the potential of the electrode at a potential ( E l ) sufficient for the reduction of oxygen permits triggering of the formation of hydroxyl radicals. Besides its simplicity, a particularly interesting point regarding this method is that it permits a controlled production of hydroxyl radicals; it is then possible to follow the formation of the different products as a function of the amount of electricity which has been used, Le., as a function of the radicals which have been produced. This paper deals with the stepwise hydroxylation of benzoic acid by hydroxyl radicals. The monohydroxylation reaction has been previously investigated by r a d i o l y ~ i s , ~and ~ - by ~ ~photoc h e m i ~ t r y . ~Radiolysis '.~~ and the Fenton reaction have also been used for the investigation of 2- or 4-hydroxybenzoic a ~ i d . ~However, ~ - ~ ~ in all these preceding investigations, the only formation of the primary hydroxylation products was observed and discussed. In the following we shall focus our attention on the formation of polyhydroxylated products by following their formation and consumption and also on the differences between the Fenton reaction and other methods used for the production of hydroxyl radicals.
Experimental Section All the products are of commercial origin and were used without further purification, except benzoic acid, which was recrystallized, and mercury, which was redistilled. Benzoic acid (BA); the monohydroxybenzoic acids (-HBA) 2-HBA, 3-HBA, and 4-HBA; the dihydroxybenzoic acids (-dHBA) 2,3-dHBA, 2,4-dHBA, 2,5-dHBA, and 2,6-dHBA; the trihydroxybenzoic acids (-tHBA) 2,3,4-tHBA and 2,4,6-tHBA; benzoquinone; resorcinol (1,3-dihydroxybenzene);and catechol (1,2-dihydroxybenzene) were obtained in the highest purity available from Aldrich. 3,4-dHBA and 3,5-dHBA as well as diethylenetriaminepentaacetate (DETAPAC) were "puriss" quality from Fluka. Femc chloride, hydroquinone, phenol (Rectapur quality), and the 0.1 M aqueous HC1 solution were obtained from Prolabo. Electrolyses were performed in a three-electrode electrochemical cell. The working electrode was a 15 cm2 mercury pool. The platinum counter electrode was placed in the anode compartment separated from the cathode compartment by a no. 4 glass frit. The reference electrode was a saturated calomel electrode (SCE). The volume of the electrolyzed solutions was 75 mL. These solutions were prepared by dissolution of 0.375 m o l (c = 5 mM) of the product to be electrolyzed in 75 mL of a 0.1 M HC1 solution (pH FZ 1). The central anodic compartment contained only the 0.1 M HCl solution. Prior to the electrolysis, dioxygen was bubbled for 15 min and then 0.012 g of FeC13 was introduced ([Fe3+] = 1 mM). When solutions with a pH lower than 2 are used, there is no necessity to introduce a complexing agent such as EDTA or DETAF'AC
10
2b
30
40
+I")
Figure 1. Gradient program.
SCHEME 2. Electrochemical Generation of Hydroxyl Radicals
TABLE 2: Composition of HPLC Solvents composition by volume eluent H20 CH,OH CH3COOH eluent A eluent B
92 61
4
4
35
4 in the solution-at such pHs the Fe2+and Fe3+do not precipitate as their hydroxides. At higher pHs (when benzoic acid is dissolved in water without buffering the solution) DETAPAC is introduced as a complexing agent to prevent the precipitation of these ions. Under such conditions, 0.1 M LiC104 is added to the anolyte and to the catholyte. In every case the solution is stirred magnetically. The potential is maintained at -0.5 V/SCE with a homemade potentiostat, a potential where both 0 2 and Fe3+ are reduced respectively to 02.- and to Fez+. The current remains constant (70 mA), which permits a constant production of hydroxyl radicals. The amount of charge passed through the solution is measured with a Tacussel IG5-N, and samples are withdrawn at regular charge intervals: 0, 50, 100, ... C. These samples are analyzed in a liquid chromatographer (Gilson) equipped with a W detector set at 280 or 3 13 nm and a Hypersil BDS C8 5 mm column (25 cm x 4.6 mm) from Shandon HPLC. In order to obtain a good separation with a reasonable elution time, a gradient of solvents was programmed with a Gilson HPLC System Manager. The composition of the solvents is shown in Table 2, and the rate was v = 0.8 mL/min. The gradient program is shown in Figure 1. Qualitative and quantitative analyses were performed with authentic samples. The calibration curves were established in a concentration range from 0.1 to 2 mM. Most of the compounds under examination absorb at 11 = 313 nm with a reasonable absorption coefficient; however, some only absorb at 280 nm. Therefore, two standards were prepared: standard 1 and standard 2 (Figure 2). Therefore the analyses performed during the electrolysis were duplicated at 313 and 280 nm and the concentration was calculated from the appropriate calibration curves.
Results and Discussion The electrochemical reduction of dioxygen leads to superoxide ion,51which is stable in an aprotic medium such as
Oturan and Pinson
13950 J. Phys. Chem., Vol. 99, No. 38, 1995
I
2H0,'
1i
+ 20,'- + H++ H,O - 20, + 2H,O, + OHk = 6 x 10"[H+]
#
pH > 6
In a strongly acidic medium (pH = 0), equilibrium 4 is displaced to the right, therefore facilitating the reduction of di~xygen.~'
i 4
m
?
0,
+ H+ + e- - HO,'
E", = -0.046 V/NHE = -0.287 VISCE (7)
As the redox potential of the Fe 3+/Fe2+couple is equal to f0.77 V/NHE (+OS3 V/SCE) when a potential (-0.5 V) is applied to the cathode under the conditions described in the experimental section, the following reactions take place:
+ 2H+ + 2e- H,O, Fe3+ + e- =+ Fe2+ Fe2++ H,O, - Fe3+ + OH' + OH0,
(8)
@
(9) (2)
The hydroxyl radical thus produced can undergo several reactions in an aqueous medium$9,55,56 among which are
OH'
+ H,O,- H,O + HO,'
OH'
+ Fe2+- Fe3++ OH-
k,, = 3.3 x lo7 M-' s-' (10) k , , = 3.0 x lo8M-'
s-l
(1 1)
+
OH' OH' -H,02
k,, = 5.3 x lo9 M-' s-'
(12)
which are in competition with the addition on benzoic acid:
OH'
+ BA -.BA(0H)'
acetonitrile (ACN), dimethylformamide (DMF), or dimethyl sulfoxide (DMSO) and in strongly basic aqueous solutions; the redox potential E o ( 0 2 / 0 2 * - ) = -0.75 V/SCE in DMSO has been measured. In a protic medium, 0 2 ' - reacts rapidly with H+ to give an unstable peroxyl radical H O i , which disproportionates to H202:52-54 0,
+ e-
--8
0,'-
-
E" = -0.33 V/NHE
= -0.572 VISCE
+ H+ HO,' pK, = 4.69 HO; + HO,' - 0, + H,O, k, = 8.3 x io5M-' HO,' + 0,'- + H,O - 0, + H,02 + OH0;-
(3)
(4)
s-'
(5)
k, = 9.7 x lo7M-' s-' (6) These reactions can be summed up as a reaction leading to the formation of H202:
S-'
(13)
The rate constant of reaction 13 is larger than that of reactions 10 and 11 but of the same order of magnitude as that of reaction 12. However, due to the low concentration of hydroxyl radicals, the hydroxylation of benzoic acid (reaction 13) will take place. The results of the hydroxylation of benzoic acid by the Fenton reagent (Fe2+ H202) and by the electrochemical Fenton reaction ( 0 2 3e2H+ catalytic amounts of Fe3+) are gathered in Table 3 and 4 and Figure 3. In the case of the chemical Fenton reaction the a-, m-, and p-isomers are in the ratio 1:1:0.5 and the yield of hydroxylated products is low (13% by reference to initial BA). On the contrary, during the electrochemical Fenton reaction at pH = 1, the yields of the different hydroxylated products vary during the electrolysis. Rather high yields of mono-, di-, or trihydroxylated products can be obtained at different times during the electrolysis (Table 4). A slight variation of the o:m:p ratio is observed from 1:1:1 at the beginning to 1:1.17:1.17 at the end of the electrolysis. These ratios can be compared with the ratios found by different authors (Table 5 ) . Examination of Table 5 indicates some variations in the relative yields of the three isomers. These variations can be assigned, in part, to the different conditions under which the experiments were performed-more acidic conditions should favor the acid-catalyzed dehydration of the hydroxycyclohexadienyl radical (Scheme 2), and there may be variations of the rate of the reoxidation of the different isomeric radicals with the oxidant but also some uncertainty in the determination of the different isomers, at a time when analytical methods were not as reliable as modern HPLC. Anyhow, even under these different conditions, the relative ratio of two isomers never
+
Figure 2. (A) Standard 1 (1= 313 nm). (B) Standard 2 (1= 280 nm). Concentration of the compounds: 0.5 mM each.
k13 = 4.3 x lo9M-'
+
+
+
J. Phys. Chem., Vol. 99, No. 38, 1995 13951
Mono- and Polyhydroxylation of Benzoic Acid
TABLE 3: Starting Material and Product Distribution (in mM) at the End of Reaction for the Fenton Reagent Hydroxylation of Benzoic Acid" BA
2342,32,53,42,3,4- 3,4,5HBA HBA HBA dHBA dHBA dHBA tHBA tHBA
3.85
0.10
0.12
0.04
0.11
0.15
0.09
'0.01
0.02
"Reaction conditions: V = 100 mL of H20; [BA]o = 5.0 mM; [DETAPAC] = 20 mM; [HzO~]= 10 mM; [Fez+] = 10 mM. Ratio of Fenton reagent to initial BA was equal to 2. Yield of hydroxylated products against BA consumed (1.15 mM) = 55%. Yield of hydroxylated products against initial BA (5 mM) = 13%.
being slightly accepting (-I),6o there will be little selectivity in the hydroxylation of benzoic acid, in agreement with the literature data of Table 5 and with the results reported in this paper. As can be observed in Figure 3, the concentration of the monohydroxylatedderivatives increases rapidly (5 x lop3mh4/ C) at the beginning of the electrolysis to reach a stationary concentration ([ZHBA] 0.6 mM, [3-HBA] = 0.7 mM, [CHBA] = 0.7 mM) at about 400 "C, at which point the net rate of formation of these compounds becomes nearly zero. At the end of the electrolysis the yield of the three HBAs starts decreasing. This can be rationalized in the following way: at the beginning of the electrolysis the main reaction is COOH
k13a
1
+ OH*
k13b
k13c
0.5
1)
Figure 3. Formation of products during the hydroxylation of benzoic acid by electrochemically generated OH' radicals.
3-HBA 4-HBA
When the concentration of monohydroxybenzoic acids reaches a sufficient value, reactions 14- 16 come into play. As the OH group is 0-,p-directing and -activating, the following reactions should be considered:
+ OH0-2,3-dHBA + 2,5-dHBA (14) 3-HBA + OH'k2,3-dHBA + 2,5-dHBA + 3,4-dHBA k14
2-HBA
exceeds two, except in one case,3o indicating a very low selectivity both in the addition of the hydroxyl radical and in the further oxidation of the hydroxycyclohexadienyl radical. This is in agreement with the ESR measurements of Schuler et al.,27 who found at pH.= 13 a ratio of 0-,m-, and p-isomers of the hydroxycyclohexadienyl radical equal to 1: 1.3:1.4. This low selectivity can be rationalized by considering the electrophilic character of the hydroxyl radical.21-25.33,55,57-58 In the case of electrophilic substitution, electron donating (+M) substituents (R) are 0-,p-directing and - a c t i ~ a t i n g . ~The ~ , ~electrophilic hydroxyl radical will selectively react with the 0- and ppositions; this is observed in the case of anisole22(R = OCH3) in the presence of an oxidant, where the ratio o:m:p of hydroxyanisoles reaches 1:0.07:0.57, and also in the case of phenol,25 where the ratio of the three diphenols is o:m:p = 1:0.17:0.75. In the case of strongly accepting substituents, Eberhardt and Y o ~ h i d ahave ~ ~ shown that the very low lying SOMO of the OH' radical interacts mainly with the HOMO of nitrobenzene, which has very small coefficients in the aromatic ring. Because of this small overlap in all ring positions, there is little selectivity in the initial addition reaction, and in the presence of a strong oxidizing agent a close to statistical distribution is observed (o:m:p= 1:0.86:0.4). The COOH group
2-HBA
(15) 4-HBA
+ OH'
k16
3,4-dHBA
(16)
The values of the rate constants k14, kl5, and k16 have been measured previously; they are gathered in Table 7. These rate constants are somewhat higher than kl3 (4.3 x lo9 L mol-' s-I), the rate constant of hydroxylation of benzoic acid. The stationary state is reached when k,,,[BA][OH'] = k14[2-HBA][OH'] k,,,[BA][OH'] = k15[3-HBA][OH']
At the end of the electrolysis when the concentration of BA becomes low, the concentration of 2-, 3-, and 4-HBA decreases. Considering the values of k14, kl5, and k16, it should be remarked
TABLE 4: Mono- and Polyhydroxylated Product Distribution during Electrolysis of 0 2 (To Generate O H ) in the Presence of Benzoic Acid" hydroxylated product concentrations in entry
Q,,,(C)
2-HBA
3-HBA
4-HBA
phenol
2,3dHBA
1 2 3 4 5 6 7 8 9
50 120 202 340 480 600 702 830 1000
0.18 0.38 0.45 0.53 0.56 0.60 0.60 0.61 0.60
0.22 0.47 0.57 0.68 0.72 0.75 0.73 0.71 0.69
0.20 0.43 0.52 0.62 0.69 0.72 0.71 0.70 0.70
trace trace '0.01 10.01 '0.01 0.01 0.01
0.02 0.06 0.12 0.18 0.26 0.37 0.43
2,4dHBA
2,5dHBA
0.02 trace 0.08 trace 0.17 '0.01 0.25
